辛伐他汀对PTHrP诱导破骨细胞形成及小鼠颅盖骨代谢的影响

目的:探讨辛伐他汀对体外甲状旁腺素相关肽(PTHrP)诱导小鼠的破骨细胞骨吸收功能的作用及其小鼠骨代谢的影响。方法:采用PTHrP诱导小鼠骨髓细胞培养破骨细胞和小鼠颅盖骨培养体系,检测辛伐他汀作用8d后破细胞骨数目和培养上清钙的变化;检测小鼠颅盖骨培养上清碱性磷酸酶和钙含量,组织学观察小鼠颅盖骨形态学变化。结果:辛伐他汀体外可明显抑制PTHrP诱导小鼠的破骨细胞骨吸收陷窝的形成及培养上清钙的释放,辛伐他汀体外可增强小鼠颅盖骨培养上清碱性磷酸酶的活性,组织学观察到辛伐他汀使小鼠颅盖骨矿化增强。结论:辛伐他汀体外不仅可促进小鼠颅盖骨的成骨活性,并且可明显抑制PTHrP诱导小鼠的破骨细胞骨吸收功能,对骨吸收性疾病有着重要的防治作用。

Effect of simvastatin on PTHrP stimulated osteoclastic resorption and anabolism of murine calvarium

Objective:To study the effect of simvastatin on PTHrP stimulated osteoclastic resorption of murine calvarium and bone anabolism in vitro. Methods:Osteoclasts were isolated from bone marrow of Balb/C mice,cultured and identified.Calvaria of the new born Balb/C mice were cultured with PTHrP at 45 ng/ml and/or simvastatin at 10~ -7 -10~ -5 mol/L for 8 d.Ca~ 2 and ALP in the culture supernatent were measured by atom spectrophotometer and automatic biochemical analyzer respectively.The bones were examined histologically.Results:Simvastatin at 10~ -7 -10~ -5 mol/L inhibited osteoclast formation and the osteoclastic bone resorption stimulated by PTHrP in vitro and reduced the release of Ca~ 2 from the cultured osteoclasts in a dose-dependent manner. Simvastatin increased the ALP activities and bone mineralization of murines calvaria cultured in vitro. Conclusions:Simvastatin may inhibit the osteoclasric resorption stimulated by PTHrP and promote bone mineralization in vitro.